Wu W M, Bodor E T, Howes J, Bodor N
Center for Drug Discovery, College of Pharmacy, University of Florida, Gainesville 32610-0497, USA.
Pharmazie. 2012 May;67(5):406-10.
The effect of delta1-cortienic acid (delta1-CA) on human skin blanching activity of the soft corticosteroid, loteprednol etabonate (LE), has been studied. Ten volunteers had applied to their forearms a dose of LE ranging from 0.1 to 1 mM, or LE from 0.1 to 1 mM in combination with 2-times the concentration of delta1-CA (0.2 - 2mM). The results indicate that delta1-CA increased LE's effect on human vasoconstriction/skin blanching activity, both in the intensity and duration. This enhancing effect of delta1-CA was also observed in other blanching studies with other corticosteroids, such as hydrocortisone. The enhancement may occur through the displacement of LE bound to transcortin (also known as corticosteroid-binding globulin, or CBG) by delta1-CA as delta1-CA has a higher affinity for CBG than that for glucocorticoid receptor (GR), resulting in more free-LE to act on GR, and increased skin blanching. In rat studies, intravenous injection of delta1-CA (5-50 mg/kg) did not affect the pharmacokinetics of LE (5 mg/kg), indicating that delta1-CA is safe for combined use with LE. In stability studies, the presence of delta1-CA at the same concentrations as LE in aqueous suspension (0.1 and 0.2%) significantly increased the stability of LE. Thus, the combination of delta1-CA with LE serves an enhancing and stabilizing role while not impacting the pharmacokinetic properties of LE.
已对δ1-皮质烯酸（δ1-CA）对软质皮质类固醇卤倍他索丙酸酯（LE）的人体皮肤变白活性的影响进行了研究。十名志愿者在其前臂上涂抹了剂量范围为0.1至1 mM的LE，或0.1至1 mM的LE与两倍浓度的δ1-CA（0.2 - 2 mM）的组合。结果表明，δ1-CA在强度和持续时间上均增强了LE对人体血管收缩/皮肤变白活性的作用。在其他使用其他皮质类固醇（如氢化可的松）的皮肤变白研究中也观察到了δ1-CA的这种增强作用。这种增强作用可能是由于δ1-CA对转运皮质素（也称为皮质类固醇结合球蛋白，或CBG）的亲和力高于对糖皮质激素受体（GR）的亲和力，从而取代了与CBG结合的LE，导致更多的游离LE作用于GR，进而增强皮肤变白。在大鼠研究中，静脉注射δ1-CA（5 - 50 mg/kg）不影响LE（5 mg/kg）的药代动力学，表明δ1-CA与LE联合使用是安全的。在稳定性研究中，δ1-CA以与LE在水悬浮液中相同的浓度（0.1%和0.2%）存在时，显著提高了LE的稳定性。因此，δ1-CA与LE的组合起到了增强和稳定的作用，同时不影响LE的药代动力学特性。
